Feng Lan, A Lisha, Bao Terigele, Mu Xiyele, Ta Na, Duan Qiang, Ta La, Chen Yongsheng, Bai Laxinamujila, Fu Minghai
Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, School of Pharmacy, Hainan Medical University, Haikou, China.
NMPA Key Laboratory for Quality Control of Traditional Chinese Medicine (Mongolian Medicine), School of Mongolian Medicine, Inner Mongolia Minzu University, Tongliao, China.
Front Pharmacol. 2023 Aug 10;14:1181133. doi: 10.3389/fphar.2023.1181133. eCollection 2023.
Gastric ulcer (GU) is one of the most prevalent digestive diseases that seriously affects people's health. Previous studies have demonstrated the anti-GU effect of Ruda-6 (RD-6), a classic formulae of traditional Mongolian medicine. However, the underlying mechanism of RD-6 against GU remains elusive. Thus, we conducted an integrative approach of network analysis, RNA-seq, and validation experiment to elucidate the therapeutic mechanisms of RD-6 in preventing GU. A network analysis was performed to predict the potential targets of RD-6. Rats were pretreated with RD-6 at different doses for 21 days, followed by GU induction with indomethacin injection. The ulcer index and inhibition rates were calculated, and the levels of inflammatory related factors were determined by ELISA. The gastroprotective mechanism of RD-6 against ulceration was verified by RNA-seq and the key pathway was detected by validation. As the network analysis predicted, RD-6 exerts anti-GU effects by regulating 75 targets and 160 signaling pathways. Animal experiment results suggested that pretreatment with RD-6 significantly ameliorated the gastric mucosal injury and inflammatory response, as evidenced by a reduced ulcer index, decreased interleukin (IL)-1β, IL-6, and IL-17 levels, and increased prostaglandin E2 (PGE2) levels in the GU model rats induced by indomethacin. RNA-seq data identified four potential hub genes that were primarily involved in the IL-17 signaling pathway. Furthermore, validation experiment showed that RD-6 inhibited the IL-17 signaling pathway by down-regulating the expression of IL17RA, proto-oncogene C-Fos (FOS), IL1B and prostaglandin-endoperoxide synthase 2 (PTGS2). Taken together, the present study provides evidence that RD-6 could effectively protect against indomethacin-induced GU, which might be attributed to suppressed inflammation. The IL-17 signaling pathway may be one of the crucial mechanisms that mediates the effect of RD-6.
胃溃疡（GU）是最常见的消化系统疾病之一，严重影响人们的健康。先前的研究已经证实了传统蒙药经典方剂如达如 - 6（RD - 6）对胃溃疡的治疗作用。然而，RD - 6抗胃溃疡的潜在机制仍不清楚。因此，我们采用网络分析、RNA测序和验证实验相结合的方法来阐明RD - 6预防胃溃疡的治疗机制。通过网络分析预测RD - 6的潜在靶点。将大鼠用不同剂量的RD - 6预处理21天，随后注射吲哚美辛诱导胃溃疡。计算溃疡指数和抑制率，并通过酶联免疫吸附测定法（ELISA）测定炎症相关因子的水平。通过RNA测序验证RD - 6对溃疡的胃保护机制，并通过验证检测关键途径。正如网络分析所预测的，RD - 6通过调节75个靶点和160条信号通路发挥抗胃溃疡作用。动物实验结果表明，RD - 6预处理可显著改善胃黏膜损伤和炎症反应，吲哚美辛诱导的胃溃疡模型大鼠的溃疡指数降低、白细胞介素（IL）-1β、IL - 6和IL - 17水平降低以及前列腺素E2（PGE2）水平升高证明了这一点。RNA测序数据确定了四个主要参与IL - 17信号通路的潜在枢纽基因。此外，验证实验表明，RD - 6通过下调IL17RA、原癌基因C - Fos（FOS）、IL1B和前列腺素内过氧化物合酶2（PTGS2）的表达来抑制IL - 17信号通路。综上所述，本研究提供了证据表明RD - 6可以有效预防吲哚美辛诱导的胃溃疡，这可能归因于炎症的抑制。IL - 17信号通路可能是介导RD - 6作用的关键机制之一。
